Neurobehavioral problems in HNRC subjects must be interpreted in the context of their medical and immunologic status. The Medical Core provides the HNRC cores and projects with quantitative, longitudinal assessment of medical history, physical signs and symptoms, immunologic status, quantitative medication histories, staging of HIV infection, and epidemiological and behavioral risk factors including sexual activity and non-medical drug exposure. It has played a leading role in conceiving, organizing, and facilitating multidisciplinary review of each visit to integrate and provide quality-control of findings from each core. To help maintain continuing subject participation in the HNRC, Medical core provides 1) individual feedback of multidisciplinary findings to participants and (with written consent) to their health care providers. 2) short term medical crisis management and referral, and 3) updates of treatment and research findings. The Medical Core has formed an Intensive Follow -Up Team to assist with long term cohort maintenance by establishing frequent monitoring of subjects with advanced AIDS. This personalized attention along with bedside assessment of subjects who are critically ill assures that subjects are studied pre-terminally and supports the neuropathological studies of AIDS. Data from the medical Core support major scientific aims of every other core and project. Furthermore, the Medical Core itself has scientific aims which include measurement and comparison of biological markers such as beta 2 microglobulin (B2M), neopterin (NEO), and quinolinic acid (QA) in blood and CSF. The role of these biological markers in evaluating immunologic status, effects of antiretroviral treatment, progression of HIV infection, and onset of central nervous system disease is under study. These markers are used ion comparison with other biologic factors (e.g. phenotype of HIV isolates from CSF) in discriminant models examining factors which produce or are associated with cognitive impairment. Specifically, the Medical Core is investigating the following hypotheses; 1) that the level of serum B2M and slope of CD4 count will predict long term risk, while level of CD4 will predict short term risk of decline in cognitive function, 2) that CSF B2M level will be linearly related to tahe degree of cognitive impairment but slope of QA will predict onset of more severe impairment in patients with AIDS, and 3) that the type and length of antiretroviral treatment will determine the relationship between CSF markers and cognitive impairment. In addition, the Medical Core will continue to explore the relationship between CSF markes and cognitive impairment. In addition, the medical Core will continue to explore the relationship of biomedical (i.e. syphilis) and behavioral (i.e. past and present substance use) cofactors to HIV- associated neurocognitive disorders.